SecY-mediated quality control prevents the translocation of non-gated porins

Abstract OmpC and OmpF are among the most abundant outer membrane proteins in E. coli and serve as hydrophilic channels to mediate uptake of small molecules including antibiotics. Influx selectivity is controlled by the so-called constriction zone or eyelet of the channel. Mutations in the loop doma...

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Autores principales:	Sebastian Jung, Verian Bader, Ana Natriashvili, Hans-Georg Koch, Konstanze F. Winklhofer, Jörg Tatzelt
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2020
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/85496819d379446e91f9fae7cfa50b28
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spelling	oai:doaj.org-article:85496819d379446e91f9fae7cfa50b282021-12-02T18:51:28ZSecY-mediated quality control prevents the translocation of non-gated porins10.1038/s41598-020-73185-y2045-2322https://doaj.org/article/85496819d379446e91f9fae7cfa50b282020-10-01T00:00:00Zhttps://doi.org/10.1038/s41598-020-73185-yhttps://doaj.org/toc/2045-2322Abstract OmpC and OmpF are among the most abundant outer membrane proteins in E. coli and serve as hydrophilic channels to mediate uptake of small molecules including antibiotics. Influx selectivity is controlled by the so-called constriction zone or eyelet of the channel. Mutations in the loop domain forming the eyelet can disrupt transport selectivity and thereby interfere with bacterial viability. In this study we show that a highly conserved motif of five negatively charged amino acids in the eyelet, which is critical to regulate pore selectivity, is also required for SecY-mediated transport of OmpC and OmpF into the periplasm. Variants with a deleted or mutated motif were expressed in the cytosol and translocation was initiated. However, after signal peptide cleavage, import into the periplasm was aborted and the mutated proteins were redirected to the cytosol. Strikingly, reducing the proof-reading capacity of SecY by introducing the PrlA4 substitutions restored transport of OmpC with a mutated channel domain into the periplasm. Our study identified a SecY-mediated quality control pathway to restrict transport of outer membrane porin proteins with a deregulated channel activity into the periplasm.Sebastian JungVerian BaderAna NatriashviliHans-Georg KochKonstanze F. WinklhoferJörg TatzeltNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 10, Iss 1, Pp 1-13 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Sebastian Jung Verian Bader Ana Natriashvili Hans-Georg Koch Konstanze F. Winklhofer Jörg Tatzelt SecY-mediated quality control prevents the translocation of non-gated porins
description	Abstract OmpC and OmpF are among the most abundant outer membrane proteins in E. coli and serve as hydrophilic channels to mediate uptake of small molecules including antibiotics. Influx selectivity is controlled by the so-called constriction zone or eyelet of the channel. Mutations in the loop domain forming the eyelet can disrupt transport selectivity and thereby interfere with bacterial viability. In this study we show that a highly conserved motif of five negatively charged amino acids in the eyelet, which is critical to regulate pore selectivity, is also required for SecY-mediated transport of OmpC and OmpF into the periplasm. Variants with a deleted or mutated motif were expressed in the cytosol and translocation was initiated. However, after signal peptide cleavage, import into the periplasm was aborted and the mutated proteins were redirected to the cytosol. Strikingly, reducing the proof-reading capacity of SecY by introducing the PrlA4 substitutions restored transport of OmpC with a mutated channel domain into the periplasm. Our study identified a SecY-mediated quality control pathway to restrict transport of outer membrane porin proteins with a deregulated channel activity into the periplasm.
format	article
author	Sebastian Jung Verian Bader Ana Natriashvili Hans-Georg Koch Konstanze F. Winklhofer Jörg Tatzelt
author_facet	Sebastian Jung Verian Bader Ana Natriashvili Hans-Georg Koch Konstanze F. Winklhofer Jörg Tatzelt
author_sort	Sebastian Jung
title	SecY-mediated quality control prevents the translocation of non-gated porins
title_short	SecY-mediated quality control prevents the translocation of non-gated porins
title_full	SecY-mediated quality control prevents the translocation of non-gated porins
title_fullStr	SecY-mediated quality control prevents the translocation of non-gated porins
title_full_unstemmed	SecY-mediated quality control prevents the translocation of non-gated porins
title_sort	secy-mediated quality control prevents the translocation of non-gated porins
publisher	Nature Portfolio
publishDate	2020
url	https://doaj.org/article/85496819d379446e91f9fae7cfa50b28
work_keys_str_mv	AT sebastianjung secymediatedqualitycontrolpreventsthetranslocationofnongatedporins AT verianbader secymediatedqualitycontrolpreventsthetranslocationofnongatedporins AT ananatriashvili secymediatedqualitycontrolpreventsthetranslocationofnongatedporins AT hansgeorgkoch secymediatedqualitycontrolpreventsthetranslocationofnongatedporins AT konstanzefwinklhofer secymediatedqualitycontrolpreventsthetranslocationofnongatedporins AT jorgtatzelt secymediatedqualitycontrolpreventsthetranslocationofnongatedporins
_version_	1718377394792824832

SecY-mediated quality control prevents the translocation of non-gated porins

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